Real World Adherence to HIV PrEP in Serodiscordant African Couples

现实世界中血清不一致的非洲夫妇对 HIV PrEP 的遵守情况

• 批准号: 8465580
• 负责人: Jessica Elizabeth Haberer
• 金额: $ 62.66万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-04 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8465580
• 关键词: AIDS prevention; Acute; Address; Adherence; Africa South of the Sahara; African; Behavior; Behavior Therapy; Build-it; Clinical Trials; Consensus; Counseling; Couples; Data; Dose; Effectiveness; Electronics; Emotional Bonds; Epithelium; Event; Fertility; Frequencies; Funding; HIV; HIV Infections; HIV Seropositivity; Health Care Costs; Heterogeneity; Heterosexuals; Individual; Infection; Intervention; Interview; Investigation; Investments; Kenya; Link; Measurement; Measures; Modeling; Monitor; Motivation; Oral; Participant; Pattern; Persons; Pharmaceutical Preparations; Phase III Clinical Trials; Placebos; Prevention strategy; Prophylactic treatment; Protocols documentation; Public Health; Recruitment Activity; Reporting; Research; Research Personnel; Risk; Sampling; Sex Behavior; Surveys; System; Tenofovir; Text; Theoretical model; Time; Trust; Uganda; United States National Institutes of Health; Vagina; Visit; Woman; Work; antiretroviral therapy; base; clinical epidemiology; cost; cost effective; cost effectiveness; design; emtricitabine; experience; high risk; improved; innovation; mathematical model; member; men who have sex with men; novel; open label; pharmacokinetic model; pill; public health relevance; scale up; sexual relationship; transmission process

DESCRIPTION (provided by applicant): Oral pre-exposure prophylaxis (PrEP) against HIV infection has demonstrated efficacy in men who have sex with men, serodiscordant couples, and young heterosexuals; however, efficacy was not shown in two studies of women. Lack of adherence is the leading hypothesis for these discrepant findings. Adherence outside of rigorous clinical trials is unknown and is essential to know in order to determine whether PrEP will be an effective public health strategy. The proposed study will determine if HIV-uninfected people in serodiscordant couples outside a clinical trial will adhere adequately enough to PrEP to be protected against HIV transmission. Approach: This study builds on our experience conducting the Adherence Sub-study within the Partners PrEP Study (a phase III clinical trial of tenofovir and emtricitabine/tenofovir PrEP) and will be integrated into a recently funded study of a public health delivery model of antiretroviral therapy-based HIV prevention strategies involving 500 serodiscordant couples in Uganda and Kenya (R01MH095507, PI: Baeten). Our Specific Aims are a follows: 1) Assess the level, trajectory, and correlates of PrEP adherence in research-naive discordant couples receiving PrEP in a public health delivery model with adherence counseling practical for scale-up; 2) Determine the relationship between patterns of adherence and risk exposure outside of a clinical trial; and 3) Determine if the level and patterns of real world adherence and risk exposure determined in Aims 1 and 2 substantially alter current estimates of PrEP effectiveness and cost-effectiveness. Innovation: We will: 1) characterize PrEP adherence in serodiscordant couples recruited into a demonstration project of PrEP delivery involving limited adherence counseling that is practical for scale-up settings; 2) use a novel conceptual framework to understand PrEP adherence behavior; 3) use text message reports of sexual behavior combined with electronic adherence monitoring to characterize temporal patterns of sexual exposure and PrEP adherence; and 4) develop models of the tenofovir drug concentration-time relationship, using prospectively collected samples, which can be used to determine which patterns of adherence are likely adequate for protection against HIV infection. Investigators: Dr. Jessica Haberer is a new investigator with significant experience studying adherence to antiretroviral therapy and PrEP in sub-Saharan Africa. Her team includes expertise in clinical epidemiology (Drs. Jared Baeten and Connie Celum), adherence measurement (Dr. David Bangsberg), qualitative analysis (Dr. Norma Ware), tenofovir pharmacokinetic modeling (Drs. Craig Hendrix and Ayyappa Chaturvedula), statistical analysis (Dr. Deborah Donnell), cost-effective modeling (Dr. Tim Hallett), and sub-Saharan African research experience (Drs. Nelly Mugo and Elly Katabira).

描述（由申请人提供）：针对 HIV 感染的口服暴露前预防 (PrEP) 已被证明对男男性行为者、血清不一致的夫妇和年轻异性恋者有效；然而，两项针对女性的研究并未显示出疗效。缺乏依从性是这些不一致的研究结果的主要假设。严格的临床试验之外的依从性是未知的，为了确定 PrEP 是否是一种有效的公共卫生策略，必须了解这一点。拟议的研究将确定临床试验之外血清不一致的夫妇中未感染 HIV 的人是否会充分坚持 PrEP 以防止 HIV 传播。方法：这项研究以我们在合作伙伴 PrEP 研究（替诺福韦和恩曲他滨/替诺福韦 PrEP 的 III 期临床试验）中进行依从性子研究的经验为基础，并将被纳入最近资助的一项抗逆转录病毒药物公共卫生交付模型研究中基于治疗的艾滋病毒预防策略，涉及乌干达和肯尼亚的 500 对血清不一致的夫妇（R01MH095507，PI：Baeten）。我们的具体目标如下： 1) 评估在公共卫生服务模式中接受 PrEP 的未接受研究的不一致夫妇的 PrEP 依从性水平、轨迹和相关性，并提供实用的依从性咨询以扩大规模； 2) 确定临床试验之外的依从性模式与风险暴露之间的关系； 3) 确定目标 1 和 2 中确定的现实世界依从性和风险暴露的水平和模式是否会显着改变当前对 PrEP 有效性和成本效益的估计。创新：我们将：1）描述血清不一致夫妇的 PrEP 依从性，这些夫妇被招募到 PrEP 实施示范项目中，该项目涉及有限的依从性咨询，这对于扩大规模的环境是实用的； 2） 使用新颖的概念框架来理解 PrEP 依从行为； 3) 使用性行为短信报告结合电子依从性监测来描述性接触和 PrEP 依从性的时间模式； 4) 使用前瞻性收集的样本开发替诺福韦药物浓度-时间关系模型，该模型可用于确定哪些依从模式可能足以预防 HIV 感染。研究人员：Jessica Haberer 博士是一位新研究人员，在研究撒哈拉以南非洲地区抗逆转录病毒治疗和 PrEP 依从性方面拥有丰富的经验。她的团队包括临床流行病学（Jared Baeten 博士和 Connie Celum 博士）、依从性测量（David Bangsberg 博士）、定性分析（Norma Ware 博士）、替诺福韦药代动力学模型（Craig Hendrix 博士和 Ayyappa Chaturvedula 博士）、统计分析方面的专业知识（Deborah Donnell 博士）、成本效益模型（Tim Hallett 博士）以及撒哈拉以南非洲的研究经验（Nelly Mugo 博士和 Elly Katabira 博士）。